Abstract

Context Pancreatic lymphoma is a rare cause of pancreatic mass, accounting for 0.5% of all pancreatic neoplasms, frequently misdiagnosed as epithelial cancer thus leading to incorrect therapeutic management. In the last few years Endoscopic Ultrasound has emerged as the most cost-effective and safe procedure and it is now recognized as the first-line procedure in the management of solid and cystic pancreatic masses. However, endoscopic ultrasound -guided fine needle aspiration diagnosis of pancreatic lymphoma remains challenging for both endoscopists and pathologists. Case report Here we present an unusual case of secondary, pancreatic, nodular involvement in a patient who suffered from a diffuse large B-cell lymphoma 3 years earlier. To better characterize this radiological finding, an endoscopic ultrasound was performed, which showed in the uncinated process of the pancreas a hypoechoic mass measuring 17 mm in diameter. A fine needle aspiration was performed in order to rule out pancreatic involvement by the known lymphomatous disease. Both the direct smears and the cellblock sections displayed an abundant, scattered population composed by monomorphous large cells with round nuclei, with multiple nucleoli acting as lymphoid centroblasts. The immunocytochemistry analysis confirmed the cytological hypothesis showing expression of CD20 and CD79a and negativity for CD3 and cytokeratin AE1/AE3. Finally, a diagnosis of pancreatic B-cell lymphoma was achieved. Conclusion pancreatic malignant lymphomas are unusual, solid tumors categorized as nonepithelial neoplasms. Endoscopic ultrasound - fine needle aspiration appears a safe, useful and valuable diagnostic modality for diagnosing pancreatic lymphoma. Moreover an important role is played by the pathologist's expertise to achieve an accurate diagnosis.

Keywords

Abbreviations

EUS endoscopic ultrasound; FNA fine needle aspiration

INTRODUCTION

Pancreatic lymphomatous involvement is a rather
unusual event: primary pancreatic lymphoma represents
a rarity, accounting for less than 2% of all lymphomas
and approximately 0.5% of all pancreatic neoplasms
[1]. Secondary pancreatic involvement during systemic
disease can occur but cytological diagnosis is very rarely
performed considering the multiorgan dissemination.
Furthermore, pancreatic involvement may be
misdiagnosed as pancreatic cancer thus leading to incorrect therapeutic management [2]. It is clear that
tissue sampling is crucial for a correct diagnosis. While
in the past pancreatic tissue sample was only achieved
by performing percutaneous biopsy or exploratory
laparotomy, recent studies have shown that fine needle
aspiration (FNA) can be used to make the diagnosis of
pancreatic lymphomas [3].

In the last few years Endoscopic Ultrasound (EUS) has
emerged as the most cost-effective and safe procedure,
and it is now recognized as the first-line procedure
in the management of solid and cystic pancreatic
masses [3]. Lymphomas can show different pattern of
pancreatic involvement, the most common being the
nodular, hypodense lesion at radiological investigations.
Lymphomatous involvement of the pancreas is usually of
the non-Hodgkin’s or B-cell type with diffuse large B-cell
lymphoma being the most common hystotype [4].

However, the diagnosis of pancreatic lymphoma with
EUS-FNA remains challenging for both clinicians and
pathologists.

Here we report an unusual case of secondary,
pancreatic, nodular involvement diagnosed by EUS-FNA
in a patient previously suffering from a diffuse large B-cell
lymphoma.

CASE REPORT

An asymptomatic 68-years-old male patient was
referred to our hospital for radiological follow-up of
lymphoma. He had been diagnosed with diffuse large B-cell
lymphoma 3 years earlier, and had obtained an excellent
response to chemotherapy. At last evaluation, peripheral
blood leukocyte count was normal and, at clinical
evaluation, there was no evidence of palpable superficial
lymph nodes. During the last follow-up, the patient
underwent a CT scan showing no lymphadenopathies and
no other neoplastic lesions at thoracic organs; however,
a doubtful enlargement of the pancreatic head was seen (Figure 1). To better characterize this radiological finding,
an EUS was performed, which showed in the uncinate
process of the pancreas a hypoechoic mass measuring 17
mm in diameter characterized by infiltrative margins, with a
central area of necrosis and ipoenhancement on evaluation
after intravenous contrast agent administration (Sonovue) (Figure 2). Moreover, a peripheral rim of edematous pancreatic parenchyma was detected. The Endoscopist
performed a FNA (3 passes, 25 G needle for direct smears
and 3 passes, 22 G needle for cellblock) in order to rule
out pancreatic involvement by the known lymphomatous
disease. In the Pathology Unit direct smears were stained
with May-Grunwald-Giemsa and with Papanicolaou stain.
The 22 G needle and syringe were rinsed and the liquid
obtained was later centrifuged. The sediment obtained was
fixed in 10% buffered formaldehyde, routinely processed
and paraffin-embedded as a cellblock. Two–micrometer–
thick sections were cut, stained with hematoxylin and
eosin (H&E). Other sections were cut and used for ancillary
studies. Immunophenotypic profiles were determined
according to standard immunoperoxidase methods. The
panel of antisera for the cellblock sections included CD20,
CD79a, CD3, and cytokeratin AE1/AE3. Both the direct
smears and the cellblock sections displayed an abundant,
scattered population composed by monomorphous large
cells with round nuclei, with multiple nucleoli resembling
lymphoid centroblasts. The immunocytochemistry
analysis confirmed the cytological hypothesis showing
expression of CD20 and CD79a and negativity for CD3 and
cytokeratin AE1/AE3 (Figure 3). Finally, a diagnosis of
pancreatic B-cell lymphoma was achieved.

Figure 1. Computed Tomography scan imaging showing the presence of a pancreatic mass in the head of pancreas.

DISCUSSION

Malignant lymphomas of the pancreas are unusual,
solid tumors categorized as non-epitehelial neoplasms,
accounting for less than 1% of pancreatic tumors and
less than 2% of extranodal lymphomas in case of primary
lymphoma [1, 2]. On the contrary, secondary pancreatic
involvement during systemic lymphoproliferative disease
can occur in up to 30% of patients even if in this setting a
predominant involvement of the pancreatic parenchyma is
uncommon [5].

In recent years, EUS with FNA has shown an important
role in the diagnosis of pancreatic lymphoma [3]. EUS
provides detailed radiological information, especially
about vascular and lymph nodes involvement by
pancreatic malignancies particularly for lesions measuring
< 20 mm, and has emerged as the most cost-effective and
safe procedure.

Moreover it enables the Endoscopist to perform FNA in
order to reach a cytological diagnosis: in this setting FNA
carried out by EUS achieves sensitivity and specificity for
malignant cytology respectively of 85-91% and 94-98%.
Despite its invasiveness, this technique is usually safe with
a complication rate (perforation, pancreatitis, infections,
tumor seeding and bleeding) of 0.28%-0.85% according to
recent studies [1, 2].

Interestingly, most of reported cases of pancreatic
lymphoma were diagnosed by EUS-FNB with 19 or FNA
with 22-gauge needle, the last one obtaining poor results
in the typization of the lymphomatous disease [4, 5, 6, 7, 8, 9]. In our case, we decided to perform FNA by using
a 25 G needle for direct smears because of the angled
position of the lesion located in the uncinate process and a
22 G needle for cellblock, obtaining an accurate diagnosis
for both direct smears and cellblock, confirming that, in
experienced hands, also a small needle is accurate and safe
for a correct diagnosis of a pancreatic mass [2, 10, 11, 12, 13].

In our case report, the patient was discovered with
an asymptomatic pancreatic mass after a remission of
lymphoma since 3 years. From an epidemiological point
of view, diffuse large B-cell represents the most common non-Hodgkin lymphoma and is characterized by frequent
extranodal involvement, which occurred in our case [1, 2].
Dissemination of lymphoma to the pancreas may display
several patterns: nodular, diffuse and multinodular, with
the nodular one being the most common form. In this
contest, lymphomatous involvement of the pancreas is
characterized by a nodular lesion visualized as hypodense
at CT scan or hypoechoic at Ultrasound (US) evaluation. This
kind of presentation poses major diagnostic challenges,
especially if devoid of anamnestic information, since
it may easily mimic the most common hystotype of
pancreatic neoplasm, adenocarcinoma. The distinction
between pancreatic adenocarcinoma and primary or
secondary pancreatic involvement by lymphoma is
crucial to plan an appropriate therapeutic treatment:
in fact, while for pancreatic adenocarcinoma surgery
represents the most important strategy, in the setting
of lymphomas chemotherapy alone can be administered
[1, 2, 14].

In our case the cytological material, using a 25 G needle
to perform an FNA, was adequate both qualitatively and
quantitatively to formulate a diagnosis. The cytological
smears were composed by large lymphoid cells resembling
centroblasts. Therefore immunochemistry was applied
on cellblock and centroblasts displayed positivity for
B-cell markers as CD20 and CD79a and negativity for
cytocheratin and T-cell marker CD3. Hence, integration of
previous anamnestic, endoscopic-ultrasound, cytological
and immunocytochemical data helped us to define this
uncommon occurrence and a final cytological diagnosis
of secondary pancreatic localization of diffuse large B-cell
lymphoma was performed [15].

CONCLUSION

In conclusion, pancreatic malignant lymphomas
are unusual, solid tumors categorized as non-epithelial
neoplasms. Primary pancreatic lymphoma is an extremely
rare entity but secondary pancreatic involvement can
occur in up to 30% of patients, although extremely rare
in case of lymphomatous remission since many years.
EUS-FNA in experienced hands was a safe, useful and
valuable diagnostic modality for diagnosing and subtyping
pancreatic lymphoma in our case. Moreover an important role is played by the pathologist's expertise to achieve an
accurate diagnosis applying ancillary techniques too, such
as immunocytochemistry especially in deceiving cases.